SERUM MYOSTATIN AND IGF-1 AS GENDER-SPECIFIC BIOMARKERS OF FRAILTY AND LOW MUSCLE MASS IN COMMUNITY-DWELLING OLDER ADULTS
SERUM MYOSTATIN AND IGF-1 AS GENDER-SPECIFIC BIOMARKERS OF FRAILTY AND LOW MUSCLE MASS IN COMMUNITY-DWELLING OLDER ADULTS
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DOI：
10.1007/s12603-019-1255-1
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发表时间：
2019-12-01
影响因子：
5.8
通讯作者：
Lim, W. S.
中科院分区：
文献类型：
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作者：
Chew, J.;Tay, L.;Lim, W. S.
目的：研究血清肌生长抑制素（绝对和标准化的总瘦质量（TBLM））和IGF-1作为老年人虚弱和低相对阑尾骨骼肌质量（RASM）的生物标志物；研究血清肌生长抑制素和IGF-1水平与虚弱和低RASM之间关系的性别差异。设计：横断面研究。背景：新加坡的“亚洲社区老年人早期肌肉减少症特征和预测虚弱和功能下降的生物标志物的纵向评估研究”（GERI-LABS）研究。研究对象：200名年龄在50岁及以上的社区居民。测量方法：使用修改后的Fried标准评估虚弱程度。根据亚洲肌少症工作组的建议，使用双能x线骨密度仪测量的高度调整后的阑尾骨骼肌质量的截止值来定义低RASM。评估合并症、认知和功能表现、身体活动和营养状况。采集的血液样本包括血清肌生长抑制素、胰岛素样生长因子1 （IGF-1）和炎症标志物（白细胞总数、CRP、IL-6和TNFaR1）。受试者分为4组：体弱/体弱伴低RASM（体弱/低RASM），体弱/体弱伴正常RASM（体弱/正常RASM），体弱伴低RASM（体弱/正常RASM），体强伴低RASM（体强/低RASM）和体强伴正常RASM（体强/正常RASM）。结果：63例（32%）受试者分为弱/低RASM， 53例（27%）分为弱/正常RASM， 28例（14%）分为强/低RASM， 56例（28%）分为强/正常RASM。与虚弱/正常RASM和健壮的受试者相比，虚弱/低RASM受试者年龄更大，BMI更低。与虚弱/正常RASM受试者相比，虚弱/低RASM受试者的平均（SE）正常化肌肉生长抑制素水平更高（1.0（0.04）对0.84 (0.05)ng/ml/kg， P=0.01）。与虚弱/正常RASM受试者相比，虚弱/低RASM受试者的中位（IQR） IGF-1水平较低(102.3,（77.7,102.5)vs 119.7 (82.7, 146.0) ng/ml， P=0.046）。肌肉生长抑制素或IGF-1在有或没有低肌肉量的健壮个体中没有差异。在以稳健/正常RASM为参照组的调整多项logistic回归模型中，整个队列中肌肉生长抑制素（P=0.05）和IGF-1 （P=0.043）与虚弱/低RASM状态相关。当按性别分层时，仅在男性中，肌肉生长抑制素与虚弱/低RASM状态显著相关（P=0.03）。在女性中，血清IGF-1与虚弱/低RASM状态相关（P=0.046），但与肌肉生长抑制素无关（P=0.53）。结论：血清肌生长抑制素，男性TBLM正常化和女性IGF-1正常化是低RASM体弱个体的潜在生物标志物，可能确定干预的目标群体。
Objectives: To investigate serum myostatin (absolute and normalized for total body lean mass (TBLM)) and IGF-1 as biomarkers of frailty and low relative appendicular skeletal muscle mass (RASM) in older adults, and;to examine gender differences in the association of serum myostatin and IGF-1 levels with frailty and low RASM. Design: Cross-sectional study. Setting: The "Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and predicting frailty and functional decline in community-dwelling Asian older adults Study" (GERI-LABS) study in Singapore. Participants: 200 subjects aged 50 years and older residing in the community. Measurements: Frailty was assessed using the modified Fried criteria. Low RASM was defined using cutoffs for height-adjusted appendicular skeletal muscle mass measured by dual-energy X-ray absorptiometry as recommended by the Asian Working Group for Sarcopenia. Comorbidities, cognitive and functional performance, physical activity and nutritional status were assessed. Blood samples collected included serum myostatin, insulin-like growth factor 1 (IGF-1) and markers of inflammation (total white cell count, CRP, IL-6 and TNFaR1). Subjects were classified into 4 groups: Frail/Prefrail with low RASM (Frail/Low RASM), Frail/Prefrail with normal RASM (Frail/Normal RASM), Robust with low RASM (Robust/Low RASM) and Robust with normal RASM (Robust/Normal RASM). Results: 63 (32%) subjects were classified as Frail/Low RASM, 53 (27%) Frail/Normal RASM, 28 (14%) Robust/Low RASM and 56 (28%) Robust/Normal RASM respectively. Frail/Low RASM subjects were older and had lower BMI compared to Frail/Normal RASM and robust subjects. Mean (SE) normalized myostatin levels were higher in Frail/Low RASM compared to Frail/Normal RASM subjects (1.0 (0.04) versus 0.84 (0.05) ng/ml/kg, P=0.01). Median (IQR) IGF-1 level was lower amongst Frail/Low RASM subjects compared to Frail/Normal RASM subjects (102.3, (77.7, 102.5) vs 119.7 (82.7, 146.0) ng/ml, P=0.046). No differences in myostatin or IGF-1 were observed among robust individuals with or without low muscle mass. In adjusted multinomial logistic regression models with Robust/Normal RASM as the reference group, myostatin (P=0.05) and IGF-1 (P=0.043) were associated with Frail/Low RASM status in the whole cohort. When stratified by gender, myostatin was significantly associated with Frail/Low RASM status in men only (P=0.03). In women, serum IGF-1 was associated with Frail/Low RASM status (P=0.046), but not myostatin (P=0.53). Conclusion: Serum myostatin, normalized for TBLM in men and IGF-1 in women are potential biomarkers for frail individuals with low RASM, and may identify a target group for intervention.